Discussion of interesting or befuddling cases related to pulmonary and critical care medicine.

Thursday, October 27, 2005

Nonresolving pneumonia

This is a bit of a long case (to make up for my lack of recent posts) that I think has an answer... See what you think. I'll post some followup later today or tomorrow.

52-year-old gentleman with a history of rheumatoid arthritis diagnosed 15 years ago for which he has been on Enbrel for the last 4 years. The manifestation of his rheumatoid arthritis was mainly joint stiffness in the hands and ankles which was completely relieved by Enbrel, and remained well controlled. He had no respiratory symptoms until 2 months ago, when he developed a dry cough. The cough worsened and then 4 weeks ago he developed high intermittent fevers. His temperatures at home were as high as 103 to 104 degrees and were accompanied by symptoms of chills and sweats. He was treated with a course of Augmentin to which he did not respond.

Prior to the onset of his symptoms he was doing work remodeling his attic and reported possible mold/fungus exposure during that time. He denies any known contacts with active tuberculosis, prior positive PPD, sick contacts, or travel.

He was then hospitalized and underwent a pulmonary embolism protocol CT scan which was negative for PE but showed a dense right middle lobe and right lower lobe infiltrate with surrounding patchy ground-glass opacity. Blood cultures were negative, 3 sputum samples were also obtained were smear and culture negative. BAL at that time was negative for acid fast bacilli, fungal, bacterial, or viral organisms. Cytology was also negative.

He was treated with intravenous antibiotics, a burst andtaper of prednisone, and his enbrel was held during his hospitalization. He underwent a repeat chest CT prior to his visit which showed no interval change in his infiltrates (see below). I initially saw him 3 weeks after his hospitalization. At that time he was on 30 mg/day of prednisone and reported that his fevers improved, but he remained severely dyspneic and continued to wear home O2 at 3 liters per minute.

Social history: He works as a utility supervisor for a university. He smoked 30-pack-years and quit when his symptoms began. His job did involve some remote asbestos exposure as well as frequent exposure to steam vault tunnels.

Additional studies:Serologic studies for histoplasmosis, blastomycosis, coccidioides,chlamydia, cryptococcus, and legionella were all negative.HIV was negative.A bone bone marrow biopsy was performed and was negative for granulomas, acid fast bacilli, fungus, or bacterial culture, and was otherwise normal.CBC, serum chemistries, and LFT’s were normal with a normal differential.

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Well, with the BAL negative for micro, this would be a noninfectious pneumonia. I would think that a neoplastic cause that is associated with airspace disease (i.e bronchoalveolar carcinoma) would be seen on the BAL - and you said cytology was negative. With his mold exposure HP would be a consideration; however the CT findings usually show an interstitial pattern, reticulonodular and ground glass. The slice you provide does show a bit of patchiness on the left side but I'm not sure if this is ground glass - hard to tell with resolution of the pic.What was the cell count? Besides lookinbg at CD8's for the above, would be nice to know what the eosinophils were.I don't know if the exposure to mold was a red-herring, but the CT and presentation are also consistent with cryptogenic organizing pneumonia....

I think the most likely thing here is RA-associated BOOP. The path would be the same, but couldn't call it COP because in this case it's associated with the RA. I suspect he just didn't get the high dose prednisone long enough. As he's had a negative BAL, I'd bump up his prednisone to 60mg/d for a few months. If there's no subjective improvement in a few weeks, I'd go for a surgical lung biopsy.

He has a persisten focal abnormality in the setting of chronic immunosuppression. When you say the BAL was negative for organisms was that on smears or are you including cultures? With negative smears I would still worry about infections, particularly TB. With his immunosuppression and underlying rheumatologic dz I would also be worried about a lymphoproliferative disorder. Any flow data as Jeff suggested?BOOP can have a restrictive pattern as in this case, and can present with assymetrical involvement.

Great comments. I thought the infiltrates were pretty dense and not along the lines of what is usually seen with HP.

No cell counts were reported on the outside bronch, and the cultures were pending when I saw him.

I was also concerned about a rheumatologic process related to RA something additional like vasculitis, Wegeners (although the CT and history are not typical). The results of his rheum w/u are listed below.

Because I was still concerned about the possibility of infection I decided to bronch him again.

So to make a complicated story more complicated- when I spoke to our pathologist about the biopsy results he said "I never seen anything quite like this in my career." A prominent lung pathologist from another institution was in agreement.

A constellation of pathologic findings are present in this case. The alveolar parenchyma manifests chronic inflammatory cell infiltrates as well as patchyfibrosis. Lymphoid aggregates are present, and many of the interstitial cells are plasma cells. Superimposed on this picture are numerous granulomas, some of which show focal necrosis and acute inflammation. A few of the granulomas appear bronchiolocentric. Rare bronchioles contain intraluminal foci of granulation tissue. Special stains are negative acid-fast bacilli and fungi.The background interstitial inflammation and fibrosis may be related to the patient's rheumatoid arthritis.

A recent publication (Modern Pathology 2005 18:651) describes a series of patients who developed persistent pulmonary infiltrates and granulomatous inflammation associated with etanercept use. The histopathologic changes noted in those patients was similar to what my patient had.

In that series, all of the patients improved with a combination of immunosuppressive therapy and discontinuing etanercept.